Characterisation of a Live-Attenuated Rabies Virus Expressing a Secreted scFv for the Treatment of Rabies

Samuel P Smith; Rebecca Shipley; Pascal Drake; Anthony R Fooks; Julian Ma; Ashley C Banyard

doi:10.3390/v15081674

Characterisation of a Live-Attenuated Rabies Virus Expressing a Secreted scFv for the Treatment of Rabies

Viruses. 2023 Jul 31;15(8):1674. doi: 10.3390/v15081674.

Authors

Samuel P Smith^{1

2}, Rebecca Shipley¹, Pascal Drake², Anthony R Fooks¹, Julian Ma², Ashley C Banyard¹

Affiliations

¹ Wildlife Zoonoses and Vector-Borne Diseases Research Group, Animal and Plant Health Agency (APHA), Weybridge, London KT15 3NB, UK.
² Institute for Infection and Immunity, St. George's Hospital Medical School, University of London, London SW17 0RE, UK.

Abstract

Rabies virus (RABV) causes possibly the oldest disease and is responsible for an estimated >59,000 human fatalities/year. Post exposure prophylaxis (PEP), the administration of vaccine and rabies immunoglobulin, is a highly effective tool which is frequently unavailable in RABV endemic areas. Furthermore, due to the constraints of the blood-brain barrier, current PEP regimes are ineffective after the onset of clinical symptoms which invariably result in death. To circumvent this barrier, a live-attenuated recombinant RABV expressing a highly RABV-neutralising scFv antibody (62-71-3) linked to the fluorescent marker mCherry was designed. Once rescued, the resulting construct (named RABV-62scFv) was grown to high titres, its growth and cellular dissemination kinetics characterised, and the functionality of the recombinant 62-71-3 scFv assessed. Encouraging scFv production and subsequent virus neutralisation results demonstrate the potential for development of a therapeutic live-attenuated virus-based post-infection treatment (PIT) for RABV infection.

Keywords: PEP; antibody; lyssavirus; rabies; rabies treatment; scFv; virus attenuation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies
Biological Transport
Humans
Rabies Vaccines*
Rabies virus* / genetics
Rabies* / prevention & control

Substances

Rabies Vaccines
Antibodies

Grants and funding

A.C.B., S.P.S. and A.R.F. were partially funded by the UK Department for Environment, Food, and Rural Affairs (Defra) and the devolved Scottish and Welsh governments under grants SE0426 and SE0431. S.P.S. was supported by a PhD studentship funded between APHA and SGUL. J.M., P.D., and S.P.S. received support from the Hotung Charitable Foundation and EU Horizon 2020 (Grant Agreement No. 774078, Pharma-Factory and Grant Agreement No. 760331, Newcotiana).